Highly efficient method for 125I-radiolabeling of biomolecules using inverse-electron-demand Diels–Alder reaction

Abstract In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans -cyclooctene group conjugated biomolecules using inverse-electron-demand Diels–Alder reaction. Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give 125 I-labeled product ([ 125 I] 1 ) with high radiochemical yield (65 ± 8%) and radiochemical purity (>99%). For radiolabeling application of [ 125 I] 1 , trans -cyclooctene derived cRGD peptide and human serum albumin were prepared. These substrates were reacted with [ 125 I] 1 under mild condition to provide the radiolabeled products [ 125 I] 6 and [ 125 I] 8 , respectively, with excellent radiochemical yields. The biodistribution study of [ 125 I] 8 in normal ICR mice showed significantly lower thyroid uptake values than that of 125 I-labeled human serum albumin prepared by a traditional radiolabeling method. Therefore [ 125 I] 8 will be a useful radiolabeled tracer in various molecular imaging and biological studies. Those results clearly demonstrate that [ 125 I] 1 will be used as a valuable prosthetic group for radiolabeling of biomolecules.